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When a varied diet is consumed, a "typical" individual has a balance of the different nutrients which includes carbohydrates, fats, proteins, minerals and vitamins. And, when the diet becomes somewhat fixed in one class of constituents at the disadvantage of another, there is enough float in the system to permit normal processes to continue. In fact it takes quite an insult to the system to provoke a disaster in which cell or organ functions are disrupted. An example of this type of result can be demonstrated with rats (since the use of humans for such purpose, would to say the least, be unethical.)
Growing rats fed an adequate diet in proteins that contain an abundance of the essential amino acids rapidly reach mature size. Their hair coat glistens, they are alert and active, they are not aggressive nor or they either obese or overly muscled. The essential amino acids are so termed because they are building blocks for all the proteins of the cell and must be supplied in the diet. Other so called non-essential amino acids are synthesized by the cells typically as degradation products of the other amino acids or are formed by minor alterations in structure which does not require complex chemistry.
When protein in the diet supplies amino acids in quantities in excess of requirements of protein synthesis, the amino acids are metabolized by a process that removes the "amino" part of the molecule resulting in a residue of carbon, hydrogen, oxygen and sometimes nitrogen or sulfur depending upon the starting amino acid. The majority are simply burned (oxidized) in processes that nature has designed to scavenger energy. However, in a few instances, the skeletal remainder from the amino acid serves as a precursor for other useful substances. In two cases, niacin and carnintine, are formed from the amino acids, tryptophan and lysine respectively. As the process for tryptophan metabolism has many interesting and well documented facets, it will be considered first.
History records that in the early days of our Republic, it was discovered that pellagra, a wasting disease occurred in those individuals that consumed diets in which corn was the major ingredient. This should have come as a surprise since corn was a basic ingredient in the diets of American Indians and yet they suffered no ill consequences. Why? Because their diet was varied and contained meats from their hunting activities and beans, squash and pumpkin seeds which also contained some life giving (or disease preventing) substance. When it was discovered that niacin the vitamin could be used to treat pellagra, it came as a surprise that meat and vegetables contain no niacin. What is then contained in these meats and seeds that is niacin like in activity. The answer was found to be tryptophan which is metabolized by the cells to form the vitamin, niacin. So, if one consumes tryptophan in abundance, a niacin deficiency is avoided as is pellagra.
Now we come to "amino acid imbalances". It is known that as proteins are consumed they are broken down to their constituent amino acids and at least a part of those amino acids are recombined to form the proteins of the cell. Typically, excesses are burned for energy. However, what happens when you add an overload of one particular amino acid? Is it destroyed to produce energy? The answer appears to be both yes and no. It somewhat involves an understanding of the rank of essential amino acids in meeting the requirements for growth. Typically, lysine is the first limiting amino acid, tryptophan is the second limiting amino acid and threonine is the third limiting amino acid., and so on. What this means is that when all the amino acids are available in abundance with the exception of lysine, growth is slowed appreciable and the animals health is threatened. Adding a small amount of lysine to the diet results in a positive response and as additional quantities are added, up to a point, growth response essentially follows a straight line.
The same follows when tryptophan is limiting. Growth is slowed, a niacin deficiency is produced and both can be reversed by the addition of "supplementary" tryptophan to the diet. In fact, if supplementary niacin is added instead of tryptophan, growth improves. This is termed a "sparing action" on the part of niacin.
With both lysine and tryptophan available in abundance, if threonine is in the diet at a low level, the same effect noted for deficiencies of lysine and tryptophan are noted, that is there is a reduction in growth. Add more threonine and the animal grows at an optimum rate. In this way, the essential amino acids were determined and their interrelationships found.
We now come to a second problem, what happens when an excess of an amino acid is consumed. As we said previously, it typically is metabolized for energy. However, if tryptophan is limited in the diet so that growth is slowed but not so much that a niacin deficiency develops, and threonine is added to the diet in a quantity in excess of that necessary for a low level of growth, something happens that at first appeared to be unexpected. The animals developed a niacin deficiency. Why? It was assumed and proven by studies of the synthesis of niacin in the cells, that greater demands for protein synthesis were made and tryptophan became limiting. Add more tryptophan and the niacin deficiency disappears, reduce threonine and the niacin deficiency disappear. This is an amino acid imbalance. In rats much affects their well being. How so for Homo sapiens? We really don't know, but it is accepted that with the evidence at hand, conversion of tryptophan to niacin would be lessened and pellagra could appear. So much for tryptophan and niacin, now let's look at the other case of an amino acid perhaps playing a role in vitamin function, the conversion of lysine to carnitine.
Carnitine was given its name based on its source from meat, i.e., carnivores (meat eaters). Actually carnitine is not only a constituent of meat but milk products and eggs as well, it is not present in vegetables. Early on it was considered as a vitamin since the definition of a vitamin is a substance required in small amounts that cannot be synthesized in the body. Carnitine fits this definition as it applies to infants, but not so well for adults because infants are unable to synthesize carnitine but adults can when adequate lysine is consumed. In the same way, one could argue that niacin is not a vitamin since the body does quite well in synthesizing niacin provided adequate tryptophan is present.
To my knowledge, no one has demonstrated the lysine-carnitine amino acid imbalance using the tryptophan model. It should be done because the consequences are wide reaching. Most vitamin supplements contain a range of vitamins of which niacin is always in supply at least equal to daily requirements. However, carnitine is not.
Is this important? Perhaps. Some textbooks (The Pharmacological Basis of Therapeutics, Goodman and Gilman, Pergamon Press) now list carnitine as a vitamin, which is one step away from recognizing that, yes, perhaps we should be paying attention to this substance that is freely available in a diet rich in meat and dairy products but lacking in those composed mostly of vegetables.
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